One of the most significant recent findings in the hearing sciences is that auditory hair cells, lost or damaged as a result of exposure to loud sounds or ototoxic drugs, can be replaced through the process of regeneration in the ears of most non-mammalian orders. As yet, there is little evidence to indicate that the new hair cells are of any functional use for hearing or of the extent to which hearing is restored. The need for information about function is particularly important given the exciting possibility that the factors, whether they be genetic or biochemical, that control and trigger such regeneration can be isolated and eventually applied clinically to reverse certain sensorineural hearing losses in humans. The overall goal of the proposed research is to document the extent to which changes in hearing function, as measured psychophysically in behaving animals as regeneration takes place, corresponds to the nature and extent of regeneration. This goal will be accomplished through 4 specific aims that use behaviorally trained quail (Coturnix coturnix) as subjects in experiments that will measure changes in absolute sensitivity (thresholds) and in frequency selectivity (psychophysical tuning curves) following either noise exposure or drug administration. Quail have been shown to regenerate hair cells throughout their life spans, and can be readily trained as subjects in psychophysical experiments. Following initial training, baseline measures will be determined from each of the behavioral subjects. They will then be exposed to damaging levels of sound or will be treated with ototoxic drugs. By comparing the results of daily behavioral tests with pre-treatment baselines, it will be possible to follow the time course of the recovery of the hearing loss, which may extend over several months. At key points throughout this period, non-behavioral cohorts that have received identical noise exposures or drug treatments will be sacrificed to allow determination of the extent to which the time course of the regeneration process corresponds to the observed recovery of hearing. In additional experiments, measures of regeneration and hearing recovery following repeated damaging noise exposures will allow assessment of the cumulative effects of such damage on the ability of the ear to repair the damage. Finally, comparison of the recovery and regeneration results following different etiologies and extents of initial damage is expected to increase our understanding of the relationship of the structure of the avian auditory system to its function, both in its normal state, as well as following regeneration.